Suppression of bacteriocin resistance using live, heterospecific competitors

Rapidly spreading antibiotic resistance has led to the need for novel alternatives and sustainable strategies for antimicrobial use. Bacteriocins are a class of proteinaceous anticompetitor toxins under consideration as novel therapeutic agents. However, bacteriocins, like other antimicrobial agents, are susceptible to resistance evolution, and will require the development of sustainable strategies to prevent or decelerate the evolution of resistance. Here we conduct proof-of-concept experiments to test whether introducing a live, heterospecific competitor along with a bacteriocin dose can effectively suppress the emergence of bacteriocin resistance in vitro. Previous work with conventional chemotherapeutic agents suggests that competition between conspecific sensitive and resistant pathogenic cells can effectively suppress the emergence of resistance in pathogenic populations. However, the threshold of sensitive cells required for such competitive suppression of resistance may often be too high to maintain host health. Therefore, here we aim to ask whether the principle of competitive suppression can be effective if a heterospecific competitor is used. Our results show that a live competitor introduced in conjunction with low bacteriocin dose can effectively control resistance and suppress sensitive cells. Further, this efficacy can be matched by using a bacteriocin-producing competitor without any additional bacteriocin. These results provide strong proof-of-concept for the effectiveness of competitive suppression using live, heterospecific competitors. Currently in-use probiotic strains or commensals may provide promising candidates for the therapeutic use of bacteriocin-mediated competitive suppression.